The cytotoxic effect of palytoxin on Caco-2 cells hinders their use for in vitro absorption studies

Palytoxin (PLTX), found in Palythoa zoanthids and Ostreopsis dinoflagellates, has also been detected in crabs and fish, through which it can enter into the food chain. Indeed, PLTX is considered the causative agent of several cases of human seafood poisoning resulting in systemic symptoms. Available epidemiological data on PLTX human toxicity suggest that the intestinal tract may be one of its in vivo targets and its potential site of access into the bloodstream. Hence, the purpose of this study was to investigate the suitability of the human intestinal Caco-2 cell line for evaluating PLTX oral absorption. A detailed analysis of PLTX cytotoxicity revealed a high sensitivity of Caco-2 cells: 4 h toxin exposure reduced mitochondrial activity (MTT assay, EC50 of 8.9 ± 3.7 × 10−12 M), cell density (SRB assay, EC50 of 2.0 ± 0.6 × 10−11 M) and membrane integrity (LDH release, EC50 of 4.5 ± 1.4 × 10−9 M and PI uptake, EC50 of 1.0 ± 0.8 × 10−8 M). After low PLTX concentration (1.0 × 10−11 M) exposure for 1-8 h, followed by 24 h recovery time in toxin-free medium, cell density reduction was only partially reversible. These results indicate that, due to the high susceptibility to PLTX cytotoxic effects, Caco-2 cells do not represent an appropriate and reliable model for investigating intestinal barrier permeation by this toxin.

► Palytoxin induces cytotoxicity in Caco-2 cells at pico - nanomolar concentrations. ► Palytoxin levels found in contaminated seafood were six order of magnitude higher. ► Caco-2 cells are not suitable to investigate palytoxin intestinal permeation.